Radiotherapy in Lung Cancer Dr. Abish Adhikari MD Resident Department of Radiation Oncology Bir Hospital/BPKMCH 1
Anatomy● Oblique fissure in both lungs.● Horizontal fissure in Right lung.● Trachea bifurcates at the level of T5.● Lymph nodes are divided into stations.● Intrapulmonary, bronchopulmonary (hilar), mediastinal, supraclavicular(scalene) nodes. 2
Epidemiology● Most common & Deadliest worldwide.● Survival at 5 years in USA is 15%.● Primary risk factor- SMOKING (~90%)● Adenocarcinoma more than Small/Squamous. (Filtered cigarette, fine particles reach periphery) 4
Presentation● Due to local tumor growth: – Centrally cough, haemoptysis, obstructive signs. – Peripherally silent, cough, pleuritic chest pain. – Nerve entrapment (LRLN, phrenic), Vascular obstruction. – Esophageal narrowing, obstruction, fistula.● Due to metastasis: – 60% SCLC, 30% - 40% NSCLC. – CNS, Bones, Liver, Adrenal Glands. 5
Overview of management in NSCLC● Surgery is the main stay for resectable and operable non small cell lung cancer● Radiation plays a role in the definitive and adjuvant management of NSCLC● Chemotherapy is an important adjuvant treatment modality, often used with radiation● Radiation along with chemotherapy are useful for palliation 8
RT in Lung Cancer: Issues● NSCLC: A moderately radio-sensitive tumor: dose escalation needed● Surrounded by organs which are dose limiting: heart, opp. lung, spinal cord, esophagus● Respiratory motion: a pertinent factor necessitating motion management in radiation delivery 9
RT in NSCLC: Stage wise• Stage: I : Surgery the mainstay; SBRT• Stage II: Surgery the mainstay; SBRT• Stage III: Surgery + RT, CT + RT• Stage IV: Palliative RT• Prophylactic cranial irradiation* 10
Adjuvant Radiation Therapy● Indicated for insufficient margins* <1cm, mediastinal nodes(N2).● 60-66Gy, 2Gy/# to the positive margin. 50 Gy/25# to probable microscopic disease.● PORT Meta analysis 21% more risk of death in post operative RT group. ● Studies since 1965, unpublished data included, Ill-defined surgical techniques, 7 of 9 trials used Co-60 unit, Crude technology of radiation therapy 11 PORT meta-analysis group Lancet 1998; 352: 257–63
Early stage NSCLC● Surgical resection: well established as the main curative treatment in stage I, II NSCLC● 5-year overall survival for (p) stage I disease: 57% to 67%● Poor PS, medical comorbidities & often preference preclude surgery in a large proportion (25%*)● 5-year survival rates with unresectable stage I, II disease treated with radiotherapy range from 15% to 30%.● 60% death due to distant metastasis ● Lancet Oncol 2009; 10: 885–94 12
● Better results with dose escalation.● Difficult to achieve with conventional radiation delivery techniques● Options now available: (A) SBRT / Cyber knife (B) Real time motion management: IGRT (C) Brachytherapy: endoluminal and interstitial 13
Patient selection criteria for SBRT in early stage NSCLC● Medically inoperable or dont want surgery● PS 0-2● Stage T1-3, N0 following PET-CT● Maximum tumor size 5cm● Not adjacent to major structures like vessels, heart, esophagus.● Able to lie flat for at least one hour 14
SBRT vs Wedge resection in Stage I NSCLC● 124 pts; T1-2N0MO● 69 wedge resections, 58 SBRT● SBRT prescribed as 48(T1) or 60(T2) Gy in 4 to 5 fractions● Median follow up of 2.5 years● No differences in DM, FFF, or CSS, but OS was higher with wedge resection at 30 months. (87% vs 72%) (Distant Metastatis, Freedom from Failure, Case Specific Survival) Journal of Clinical Oncology, Vol 28, No 6 , 2010: pp. 928-935 15
Brachytherapy for early stage NSCLC● Endobronchial (endoluminal) brachytherapy● Interstitial brachytherapy 16
NSCLC : Definitive RT● Stage III: – Main bulk of the disease. – 60 – 75 Gy to the gross disease (RTOG 73-01) – 50 Gy to the microscopic disease – Hyperfractionation showed better roles. – 69.6 Gy . 1.2Gy/# , 2#/day. Best survival rates (20% at 3 years) – CHART (Continuous Hyperfractionated Acclerated Radiotherapy) : 1.5Gy/#. 3#/day. 36#. Total: 54Gy – RT vs CT/RT Benefit: 2 months (at 3 years) Ann Intern Med. 1996;125:723-729. 17
RT Techniques: 2D Planning● 2 cm margin around any gross tumor.● 1 cm margin around regional LN groups.● Upper lobe tumor: B/L supraclav & subcarina.● Middle lobe tumor: Entire mediastinum (thoracic inlet to 8 cm below carina)● Lower lobe tumor: Entire mediastinum from thoracic inlet to diaphragm. 18
CTV ● Contains gross and microscopic disease. ● GTV-to-CTV : 6 mm for squamous cancers 8 mm for adenocarcinomas to cover the gross tumor and microscopic disease with 95% accuracy. For others, 8mm. ● In the absence of radiographic proof of invasion, CTV of primary lesion should not extend into the chest wall or mediastinum. ● CTV expansions of lymph node disease should not extend into the major airways or lung.Giraud P et al. Evaluation of microscopic tumor extension in NSCLC for 3D-CRT planning. 23Int J Radiat Oncol Biol Phys 2000;48:1015-1024.
PTV● CTV + margin for daily setup error and target motion.● 4D CT study, 50% of the tumor moves > 5 mm 13% moves > 1 cm (more when near diaphragm)● Individual assessment is recommended.● Breath holding, Gated techniques.● ITV : Only takes the organ movements. 24 ICRU 62
Dose and volume ● Gross disease i.e. primary and involved nodes: 65-70 Gy (+/- CT) ● Elective nodal irradiation not recommendedMore radiation pneumonitis with ENI (29% vs.17%, P = 0.044 ). 25
RTOG 1106 Required OARsStructure InstructionsLung Both lungs should be contoured using pulmonary windows. The right and left lungs can be contoured separately, but they should be considered as one structure for lung dosimetry. All inflated and collapsed, fibrotic and emphysematic lungs should be contoured, small vessels extending beyond the hilar regions should be included; however, GTV, hilars and trachea/main bronchus should not be included in this structure.Heart The heart will be contoured along with the pericardial sac. The superior aspect (or base) will begin at the level of the inferior aspect of the pulmonary artery passing the midline and extend inferiorly to the apex of the heart. 26
Esophagus The esophagus should be contoured from the beginning at the level just below the cricoid to its entrance to the stomach at GE junction. The esophagus will be contoured using mediastinal window/level on CT to correspond to all muscular layers out to the fatty adventitia.Spinalcord The spinal cord will be contoured based on the bony limits of the spinal canal. The spinal cord should be contoured starting at the level just below cricoid (base of skull for apex tumors) and continuing on every CT slice to the bottom of L2. Neuro formanines should not be included.Brachial This is only required for patients with tumors of upperplexus lobes. Only the ipsilateral brachialplex is required. This will include the spinal nerves exiting the neuro foramine from top of C5 to top of T2.. 27
Dose-Volume ConstraintOrgan RT Alone Chemo/RTCord 50 Gy 45 GyLung MLD <20 Gy MLD <20 Gy V20<40% V20 <35% V10 <45% V5 <65%Heart V40 <50% V40 <50%Esophagus Dmax <75 Gy Dmax <75 Gy V60 <50% V55 <50%Kidney 20 Gy (<50% of combined both kidneys or <75% of Same as RT one side of kidney if another kidney is not functional)Liver 30 Gy (<40%) Same as RT 47 M.D. Anderson
IMRT● Dose escalation without big dose to surrounding tissue.● Benefits in Prostate and Head & Neck.● Scientists were skeptical about IMRT in Lungs due to assumption that IMRT may deliver low yet damaging doses to a larger volume of normal lung tissue.● Movement of a tumor because of respiration introduces another level of complexity to both the IMRT dosimetry and the technique used. 48
IMRT ● Found that IMRT may be more suitable than 3D CT treatment planning for cases of advanced-stage disease with a larger GTV. ● Median absolute reduction of lung volume irradiated above 10 and 20 Gy were 7% and 10%, respectively. ● >2 Gy less mean total lung dose and 10% decrease in the risk of radiation pneumonitis. ● Heart, Esophagus, thoracic tissue dose decreased.Liu H, Wang X, Dong L, et al. Feasibility of sparing lung and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lungcancer. Int J Radiat Oncol Biol Phys 2004;58:1268-1279. 49Murshed H, Liu H, Liao Z, et al. Dose and volume reduction for normal lung using intensity-modulated radiotherapy for advanced-stage non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2004;58:1258-1267.
IMRT ● Tumors in the superior sulcus or close to the esophagus or spinal cord or patients with positive lymph nodes may benefit more. ● Earlier-stage, small mobile tumors may not be good candidates for IMRTChang J, Liu H, Komaki R. Intensity modulated radiation therapy and proton radiotherapy for non-small cell lung cancer. Curr 51Oncol Rep 2005;7:255-259.
Proton Beam ● Well-defined range of penetration. ● By modulating the Bragg peak across the target volume, proton beams can deliver a full, localized, uniform dose of energy to the treatment site while sparing the surrounding normal tissues. ● In combination with IGRT. ● Results comparable to surgery in stage IA.Shioyama Y, Tokuuye K, Okumura T, et al. Clinical evaluation of proton radiotherapy for non-small-cell lung cancer.Int J Radiat Oncol Biol Phys 2003;56:7-13. 52
Superior sulcus tumors● Preoperative RT f/b extended surgical resection: most common treatment.● Radiotherapy: a primary treatment, for inoperable superior sulcus tumors● Palliation of pain in up to 90 percent of the patients.● Doses of 20 to 80 Gy have been used● A dose of at least 60 Gy is recommended for primary radiotherapy. NEJM, 1997, 337(19): 1370-76 57
Small Cell Lung Cancer● Limited disease: confined to the hemithorax.● Extensive : extends beyond the hemithorax.● Most of the improvement in outcome was attributed to more effective combination chemotherapy regimens.● Locoregional therapy alone, either surgery or RT, improved the short-term survival only slightly.● Role of RT proven once distant metastasis was controlled & local failure was apparent. 58
Small Cell Lung Cancer ● Thoracic RT and Prophylactic Cranial Irradiation. ● TRT concurrent with chemotherapy. ● Early TRT showed better outcome than late. ● Accelerated hyperfractionation better than daily fractions ( 5yr survival 28% vs 21%) ● No significant difference in local tumor control or survival with treatment between 45 Gy and 65 Gy when effective chemotherapy was given. 59Murray N, Coy P, Pater JL, et al. Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lungcancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1993;11:336-344.
Prophylactic Cranial Irradiation Brain metastases -10% at presentation - 80% at 2 yrs* Irradiation of entire intracranial contents Lower border at C2-3 vertebra Doses 24 – 30 Gy @ 3 Gy/# Increased the 3 year survival from 18% to 26% # 60*Cancer 1979:44;1885-1893 #Ann Oncol 2002;13:748-54